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J Geriatr Oncol. Author manuscript; available in PMC 2018 July 01.
Published in final edited form as:
J Geriatr Oncol. 2017 July ; 8(4): 308–314. doi:10.1016/j.jgo.2017.04.001.

Cardio-Oncology in the Older Adult

Prajwal Reddy, M.D.1, Chetan Shenoy, M.B.B.S.2, and Anne H. Blaes, M.D., M.S.3
1
Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
2
Cardiovascular Division, Department of Medicine, University of Minnesota Medical Center,
Minneapolis, Minnesota, USA
3
Division of Hematology, Oncology and Transplantation, Department of Medicine, University of
Minnesota Medical Center, Minneapolis, Minnesota, USA

Abstract
Heart disease and cancer are the leading causes of death in older adults. Many first-line cancer
treatments have the potential for cardiotoxicity. Age-related risk factors, pre-existing cardiac
disease, and a high prevalence of comorbidities are reasons for increased cardiotoxicity in older
adults. Concerns regarding cardiotoxicity may lead to frailty bias and undertreatment, resulting in
suboptimal outcomes. There is an urgent need for geriatric-specific evidence and guidelines to
help tailor care for this vulnerable group. A multi-disciplinary approach based on close
collaboration between oncologists, cardiologists, and geriatricians, among other specialist
clinicians is essential.

Keywords
Cardio-oncology; geriatrics; older adult; cardiotoxicity; cardiotoxic treatments

Introduction
Cardio-oncology is an area of growing interest in recent years. Data are lacking on
cardiooncology specific to older adults. This is increasingly becoming important as advances
in cancer treatments result in longer patient survival (1). The 5-year survival of patients
diagnosed with cancer has steadily increased from 49% to 69% over the past three decades
(1). The proportion of cancer survivors that are 65 years or older has increased
exponentially. By 2020, it estimated that the number of cancer survivors will increase by
31% to 18 million, and that two-thirds of all cancer survivors will be 65 years or older (2–4).
As the incidence of cancer rises with increasing age, so does the prevalence of
 Reddy et al. Page 2

Address for Correspondence:

Author ManuscriptAuthor Prajwal Reddy, M.D.,
ManuscriptAuthor Department of Medicine, University
ManuscriptAuthor Manuscriptof Minnesota, 420 Delaware Street, S.E.,
MMC 284, Minneapolis, MN, USA 55455, reddy158@umn.edu.
Disclosures and Conflict of Interest Statements
The authors have no conflicts of interest to disclose.
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cardiovascular disease (CVD). Those older than 65 years account for more than half of CVD
hospitalizations and approximately 80% of deaths (5). Even more striking, those 75 years of
age or older account for 50% of cardiovascular deaths despite accounting for only 6% of the
population (5).

Despite the increased prevalence of older adults living with cancer and associated treatment
toxicities, patients 65 years or older are underrepresented in clinical trials (5–7). Older
patients are frequently offered lower doses of chemotherapy due to concerns of toxicity,
presumed frailty, and the high likelihood of coexisting comorbidities. Several observational
studies have noted poorer outcomes in this group possibly due to undertreatment and
agerelated factors (8, 9). As a result, optimal care of older adults with cancer necessitates
evidence-based and guideline-directed care specific to this vulnerable group. Such care is
especially critical for elderly patients at risk for cardiotoxicity.

Risk Factors of Cardiotoxicity

The 2016 American Society of Clinical Oncology (ASCO) Clinical Practice Guideline for
the prevention and monitoring of cardiac dysfunction in survivors of adult cancers identifies
the following risk factors for cardiac dysfunction: older age (age greater than 60 years),
high-dose anthracycline therapy, high-dose radiotherapy, cardiovascular risk factors
including smoking, diabetes, dyslipidemia, and obesity, borderline low cardiac function,
valvular disease, and history of myocardial infarction (10). An estimated 80% of patients 60
years of age or older have at least one comorbid condition and 50% have two or more (11).
In patients older than 80 years, as many as 70% have multiple comorbid conditions (11). In a
retrospective analysis of patients receiving treatment for acute myeloid leukemia, a larger
proportion of patients older than 60 years had significant comorbidities compared with those
younger than 60 years (58.3% vs. 26.3%) (12). Not surprisingly, these comorbidities include
diabetes mellitus, chronic obstructive lung disease, chronic kidney disease, and pre-existing
heart disease (12). The cumulative effect of these factors, as illustrated in Figure 1 and
previously described by Shenoy et al. (13), can be described as a “snowball effect.” The
“snowball,” formed of baseline age-related factors is “set in motion” by the cancer diagnosis
and is further exacerbated by cancer treatments which cause direct injury to tissues and
organs. Polypharmacy and use of potentially inappropriate medications are prevalent in
older adults and can exacerbate the toxicity associated with cancer treatments (14–16). A
multidisciplinary approach, including pharmacist involvement, is vital to preventing
polypharmacy and inappropriate medication-related toxicities. Medication therapy
management (MTM), consisting a thorough review of medications by a pharmacist, is
increasingly being adopted in older patients and those with multiple comorbidities, including
those with cancer (17). A growing number of retrospective studies indicate that MTM
significantly reduces drug-drug interactions, adverse drug events, and non-adherence in
older patients with cancer (17, 18).

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Cancer Treatment-Specific
Author ManuscriptAuthor ManuscriptAuthorConsiderations
ManuscriptAuthor Manuscript
Comprehensive reviews exist on the cardiac toxicity of chemotherapy agents (10, 19, 20); in
this article, cancer therapies with the highest risk for cardiotoxicity in the elderly population
are discussed below including anthracyclines, trastuzumab, tyrosine kinase inhibitors,
fluoropyrimidines, and radiation therapy.

Anthracyclines
Anthracyclines remain the first-line therapy for many cancers including breast cancer,
hematological cancers, and sarcoma. They are incorporated in more than 50% of treatment
regimens for these cancers (21, 22). They are also the most commonly associated cancer
drugs known to cause irreversible dose-dependent cardiotoxicity. In a meta-analysis by
Smith et al., an anthracycline-based regimen was associated with a higher risk of
cardiotoxicity with an odds ratio of 5.43 compared with a non-anthracycline regimen (21).
Around 75% of patients with anthracycline-related left ventricular systolic dysfunction do
not have full recovery to normal function (23). The incidence of heart failure has been
estimated at 2% at 200mg/m2, 5% at 400 mg/m2, 16% at 500 mg/m2, and 26% at 550
mg/m2 (24, 25). ASCO guidelines estimate a 1.6 to 6.8-fold increased risk of cardiac
dysfunction in elderly patients, defined as 60 years of age or older, when compared to
younger patients with cancer (10). Furthermore, studies limited to patients 65 years of age or
older, were noted to have increasing risk of cardiac dysfunction with age (10). Elderly
patients may be more susceptible to cardiotoxicity due to their age-related decrease in
myocardial volume from cardiomyocyte loss and an increase in interstitial fibrosis. A study
using cardiovascular magnetic resonance imaging (CMR) demonstrated that left ventricular
mass has an inverse relationship with anthracycline dose and is a predictor of major adverse
cardiovascular events (26). Therefore, elderly patients with a lower baseline myocardial
volume may especially be vulnerable for cardiotoxicity, further loss of myocardial volume,
and consequently, increased adverse cardiovascular outcomes. No specific recommendations
regarding dose reductions can be made due to sparse data on cardiac dysfunction and left
ventricular volume. A cumulative dose greater than 450 mg/m2 is generally limited due to
the risk of cardiac dysfunction, and most oncologists typically attempt to limit doses above
300 mg/m2 if possible in patients of all age groups (27). Although no guidelines are
currently set for an upper limit of anthracycline dose in older patients, it may be prudent to
have lower limits in elderly patients identified at risk for cardiotoxicity (27). Several
randomized control trials have evaluated different formulations of anthracyclines in order to
minimize cardiotoxicity (28–30). Continuous infusions of epirubicin and doxorubicin are
associated with lower cardiotoxicity when compared with a bolus infusion (30). Similarly,
studies have demonstrated lower cardiotoxicity with epirubicin when compared with
doxorubicin. Liposomal doxorubicin has been shown to have decreased cardiotoxicity while
maintaining efficacy in randomized control trials (28–30). A single-arm phase II multicenter
trial evaluated liposomal doxorubicin for treatment of large B-cell lymphoma in 80 patients
aged 60 years or older (28). Cardiac events defined as Common Terminology Criteria for
Adverse Events (CTCAE) Grade 3 or higher, were observed in only 4%, with an
asymptomatic decline in left ventricular systolic function noted in 20% (28). While this
study did not compare liposomal doxorubicin to standard doxorubicin, previous studies have
documented significantly higher cardiac toxicity in older patients receiving standard

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Author ManuscriptAuthor doxorubicin-containing

ManuscriptAuthor regimens. In the CAPRICE
ManuscriptAuthor study of elderly or cardiotoxicity-prone
Manuscript
patients with high-risk breast cancer, a regimen including liposomal doxorubicin,
cyclophosphamide, and paclitaxel resulted in no significant decrease in left ventricular
systolic function while achieving a pathological complete response rates comparable to
regimens with standard doxorubicin (29).

Although not specifically in elderly patients, dexrazoxane infusion before anthracycline

therapy has been demonstrated to mitigate cardiotoxicity (31, 32). A multicenter, phase III
trial of a 164 patients with breast cancer showed a 39% versus 13% fewer cardiac events and
11% versus 1% incidence of heart failure in those treated with dexrazoxane versus no
dexrazoxane; treatment efficacy was similar (33). Further studies are needed on the use of
dexrazoxane for the prevention of cancer treatment-related cardiotoxicity in the elderly.

Trastuzumab
Trastuzumab is frequently used in the therapy for breast cancer and in a growing number of
other cancers which overexpress human epidermal growth factor 2 or HER2 neu. In these
tumors, treatment with trastuzumab greatly improves outcomes; trastuzumab, however, also
has the potential to cause cardiotoxicity manifested as left ventricular systolic dysfunction.
The incidence of cardiotoxicity has been estimated anywhere between 2% to as high as 26%
(34–36) and has been noted to be independent of the cumulative dose. The broad range in
incidence speaks to the varied regimens used including monotherapy, in combination with
taxanes, and in combination with anthracyclines, where it has the highest incidence (35). In
a large population study of 9,535 patients with a median age of 71 years, those treated with
trastuzumab had an overall increased incidence of cardiotoxicity when compared with those
not treated with trastuzumab - 29.4% versus 18.6% (35). Furthermore, a competing risk
regression model utilizing patients aged 66–70 years as the reference category, noted an
incremental increase in risk of cardiac dysfunction with age, noting the highest risk in those
76 years of age or older and those with pre-existing comorbidities (35). Despite the concern
for cardiac toxicity, trastuzumab continues to be frequently used due to its high efficacy in
treatment of HER2-positive breast cancer (37–39). Advancing age is a risk factor for
developing cardiac dysfunction; however, shortening therapy is not recommended in this
group due to the therapeutic benefit in breast cancer. Screening recommendations are
discussed later in this article. In those with evidence of cardiac dysfunction following
therapy, following thorough review of benefits and risk of treatment, decision to discontinue
or hold treatment should be made by the primary oncologist in close collaboration with a
cardiologist.

Fluoropyrimidines
Fluoropyrimidines are associated with the risk cardiotoxicity estimated between 4–7% and
consisting of angina, hypertension, arrhythmia (19). The most common toxicity is anginal
chest pain, but myocardial infarction, arrhythmias and heart failure have also been reported
(19). One small study estimated a 5.5 times higher risk in patients with pre-existing cardiac
comorbidities (40). A dose-dependent toxicity is observed, and patients with pre-existing
cardiac risk factors are at increased risk (19, 40). Fluoropyrimidine-related cardiotoxicity

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 Reddy et al. Page 5

Author ManuscriptAuthor can also recur with rechallenge.

ManuscriptAuthor Older patients areManuscript
ManuscriptAuthor at risk for this toxicity due to the
increased prevalence of cardiovascular risk factors in this age group.

Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKI) are small molecule inhibitors that are used in targeted
therapy directed at specific cell signaling pathways in several cancers (41). Lapatinib, a TKI
inhibits HER2 kinase which is in the same pathway as trastuzumab, but has a decreased risk
of cardiotoxicity when compared with trastuzumab (34). In a meta-analysis of 44 clinical
studies, 1.6% of 3,689 patients treated with lapatinib were noted to have cardiotoxicity
defined as asymptomatic decline in left ventricular systolic function, which was ultimately
reversible (19, 34, 42, 43). Other TKIs such as sunitinib and sorafenib have reported
cardiotoxicities as high as 11% including an asymptomatic decrease in left ventricular
systolic function and a small proportion with heart failure (44–46). It is unclear whether
potential cardiotoxicities are shared by the class of drugs or are specific to the molecule
inhibited. Current evidence, including the studies above, have seldom outlined toxicities by
age, and have primarily assessed younger patient groups. More clinical studies are needed to
assess cardiotoxicity in older patients receiving these novel agents (10, 19).

Radiation Therapy
Radiation therapy, which is often used in Hodgkin lymphoma and breast cancer, may be
followed by cardiotoxicity including radiation-induced coronary artery disease, valvular
disorders, constrictive pericarditis, and cardiomyopathy (47). In a population-based,
casecontrol study of 2,138 patients with breast cancer treated with left-sided or right-sided
radiation therapy there was an increase in ischemic heart disease and major coronary events
with a linear increase of major coronary events with the dose of radiation, within the first
five years and at least 20 years after radiation therapy (48). Of note, the proportional
increase in major coronary events was similar in women with and without cardiac risk
factors at the time of therapy, but was overall higher in patients with pre-existing cardiac
disease. Not surprisingly, there was also an increase in major coronary events in older
patients especially those with pre-existing cardiac risk (48). In a large registry-based study
using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)
program of 27,283 women, patients that received radiation therapy between the years 1973–
1979 for left-sided compared with right-sided breast cancer had a statistically significant
increase in ischemic heart disease (49). In subsequent years, 15-year mortality from
ischemic heart disease decreased from 13% in patients treated in the mid-1970s to 5.8% in
the late 1980s and there was no statistically significant difference between left- and
rightsided breast cancers (49). The authors concluded these results were secondary to
improved shielding and decreased radiation doses over the years (49). While this is
encouraging, there are few data specific to the elderly patients on the risk-stratification for,
and administration of radiation therapy.

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PreventionManuscriptAuthor ManuscriptAuthor Manuscript

Author ManuscriptAuthor
Multi-disciplinary Approach to Care of the Older Patients with Cancer
An individualized assessment of patient risk factors is critical in preventing cancer
treatment-related complications. Often overlooked, chronologic age is not a reliable
indicator of potential comorbidities or frailty (50). Undertreatment and poorer cancer-related
outcomes are dangers of using absolute age as a definitive guide for treatment. Use of a
comprehensive geriatric assessment (CGA) in the care of elderly patients has the potential to
improve outcomes and aid in risk stratification. In recent years, many have advocated for a
multi-disciplinary approach including oncologists, cardiologists, pharmacists, and
geriatricians (20). Studies evaluating CGAs typically focus on factors such as functional
status, cognitive abilities, emotional conditions, comorbid conditions, nutritional status,
polypharmacy and environmental situation (51). Standard oncologic evaluations such as the
Eastern Cooperative Oncology Group (ECOG) scale and the Karnofsky Performance Scale
(KPS) have been noted to poorly predict treatment-related complications in elderly patients
(52). In a study by Ghosn et al., an abridged geriatric assessment, incorporating the factors
listed above, performed better than the Karnofsky Performance Scale (KPS) and the
Physical Performance Test (PPT) in predicting mortality in elderly patients with cancer (52).
In a recent consensus statement, the International Society of Geriatric Oncology has
recommended incorporating the factors listed above into routine geriatric assessments, but
did not find sufficient evidence to recommend any one particular CGA (53). Similarly, the
National Comprehensive Cancer Center guidelines have a separate section on the older
patient outlining the importance of risk factor assessments in the aging population,
particularly related to cardiac toxicity (54). There is a need for evidence on the role of
geriatric assessments for risk stratification and on effective ways to incorporate them into
routine oncologic practice (55).

Identification of The Higher Risk Older Patient

Risk stratification remains difficult in elderly patients at risk for cardiotoxicity. A
comprehensive evaluation of cardiovascular comorbidities such as hypertension, diabetes,
dyslipidemia, and smoking need to be evaluated prior to start of therapy (27). Those patients
receiving high-dose anthracyclines, high-dose radiation, and history of prior cardiac disease
are at greatest risk for cardiac dysfunction are at highest risk for cardiotoxicity (10).
Cancerspecific mortality is often higher in older patients, likely due to the impact of age-
related factors (35, 56). Evidence from observational studies suggests possible
undertreatment, as elderly patients are frequently offered lower doses of chemotherapy due
to concern for cardiotoxicity (8, 57). Additionally, alternative treatments exist in some
instances, data continue to show significantly better cancer-specific outcomes with first-line
treatments such as anthracyclines and trastuzumab in some patient populations (9, 58–61).
This finding highlights the balance that is needed between minimizing cardiotoxic therapies
and improving cancer-specific outcomes by identifying high risk elderly patients.

Pre-treatment evaluation of left ventricular systolic function is a standard part of many

treatment protocols and current SIOG recommendations. However, the utility of this
approach has been debated due to a low prevalence of asymptomatic left ventricular systolic
dysfunction, with this strategy missing most patients that will ultimately have cardiotoxicity
(62). Serum biomarkers may be useful in predicting cardiotoxicity and the role of baseline

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 Reddy et al. Page 7

Author ManuscriptAuthor assessment of serum biomarkers

ManuscriptAuthor prior to cancer treatment
ManuscriptAuthor in predicting cardiotoxicity is
Manuscript
being evaluated (63). Imaging biomarkers are also promising, and the role of pre-existing
fibrosis on CMR to predict cardiotoxicity is currently being investigated (64).
A study utilizing the SEER database validated a risk score to help identify a those at risk for
heart failure or cardiomyopathy in patients of all ages receiving trastuzumab (65). Patient
were stratified into low, intermediate, and high risk; while incorporating readily accessible
risk factors such as age, chemotherapy type, coronary artery disease, atrial fibrillation/flutter,
diabetes mellitus, hypertension, and renal failure (65). Similar risk score assessments should
be studied to aid in a more objective assessment of risk in older patients receiving other
cardiotoxic therapies.

Medications
Small randomized controlled trials have evaluated the utility of using mainstays of heart
failure therapy, renin angiotensin inhibitors, aldosterone inhibitors and beta-blockers, as
preventive therapy for chemotherapy-related cardiotoxicity (31, 66–71). None of these
studies looked solely at older patients, but neither were they excluded. The OVERCOME
trial looked at a small randomized control group of 90 patients (mean age 50 years)
diagnosed with hematologic cancers and demonstrated prevention of left ventricular systolic
dysfunction in those treated with prophylactic enalapril and carvedilol, compared with
placebo (70). The PRADA trial, a randomized controlled trial comparing candesartan and
metoprolol in patients treated for early breast cancer with anthracyclines and trastuzumab,
indicated a protective effect of candesartan against left ventricular systolic dysfunction
without a similar benefit for metoprolol (72). In the MANTICORE 101-Breast trial,
perindopril and bisoprolol each attenuated trastuzumab-related declines in left ventricular
systolic function, but did not prevent concurrent left ventricular remodeling, which was the
primary outcome measure (73). In a double-blind, placebo-controlled study of
spironolactone given simultaneously with anthracycline therapy, spironolactone had a
protective effect in the development of left ventricular systolic dysfunction (71). Despite the
favorable evidence presented above, routine prophylactic use of these therapies for
cardiotoxicity is limited by the lack of consensus, as noted in two meta-analysis with
differing conclusions on the benefits of these preventive strategies (32, 74). This is likely
because of the heterogeneous nature of the studies included in the meta-analyses and the
small numbers in each individual trial. There are several ongoing clinical trials with no
upper limit for age evaluating the utility of beta blockers, ace inhibitors, and statins in
prevention of chemotherapy induced cardiotoxicity (75–79).

Although, prophylactic use of these medications has limited evidence currently, treatment of
risk factors such as diabetes, hypertension, hyperlipidemia and smoking are important
considerations (10). Aggressive treatment of hypertension utilizing beta-blockers,
ACEinhibitors, and ARBs should be considered in patients receiving cardiotoxic therapies.

Exercise
Aerobic exercise has evidence suggesting its use for anthracycline-induced cardiac injury as
a preventive and treatment strategy (80). The evidence supporting exercise is well
established in pre-clinical animal studies, noting aerobic exercise as an effective

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 Reddy et al. Page 8

Author ManuscriptAuthor prophylactic method in prevention

ManuscriptAuthor of left ventricular
ManuscriptAuthor systolic dysfunction (80). Studies in
Manuscript
humans have documented improvements of psycho-social parameters in patients receiving
cancer treatment (81). Studies investigating the effects of exercise training during breast
cancer treatment on prevention of cardiotoxicity are limited. The only study on this topic, by
Haykowsky, et al., showed that aerobic training did not prevent trastuzumab-related left
ventricular remodeling or decline in left ventricular ejection fraction after four months of
treatment in women with HER2-positive breast cancer (82).

Surveillance
Imaging
Current recommendations for imaging surveillance include monitoring of left ventricular
systolic function during treatment with both anthracyclines and trastuzumab. Current
National Comprehensive Cancer Network guidelines suggest cardiac monitoring at baseline,
three, six, and nine months after initiating therapy for trastuzumab therapy, upon completion
of treatment, and every six months for two years following completion of treatment (83).
Additionally, the current International Society of Geriatric Oncology (SIOG) guidelines
recommended regular monitoring of left ventricular systolic function with echocardiography
or multiple gated acquisition scanning (MUGA) every two to three cycles of anthracyclines
in patients 70 years of age or older (19, 27). Further attention is needed in those who have an
LVEF drop of 10% even if it remains within the normal range (27). Early identification of
left ventricular dysfunction is vital to stop worsening and to identify patients that may
benefit from cardioprotective treatments. In a prospective study of 2625 patients with no
upper age limit and median age of 51, observed a dose-dependent cardiotoxicity in patients
receiving anthracyclines most often within the first year of treatment, along with the
observation that close monitoring allowed for early detection and treatment of cardiotoxicity
(23). The authors hypothesized, early identification of left ventricular dysfunction, in a
potentially reversible phase of injury, allowed for early start of heart failure therapies and
recovery of baseline LVEF (23).

Novel echocardiographic techniques are gaining traction as possible early predictors of

cardiotoxicity. In cross-sectional studies, tissue Doppler imaging showed promise as an early
predictor of adverse cardiac outcomes prior to onset of left ventricular dysfunction (72, 84).
Myocardial deformation (strain) has garnered increasing interest as an early predictor of left
ventricular systolic dysfunction. In an expert consensus statement, Plana et al., advocate for
global longitudinal strain (GLS) as the optimal parameter for early detection of sub-clinical
left ventricular dysfunction (85). Cardiac fibrosis identified using CMR also holds promise
for the early detection of cardiotoxicity and warrants further study (86). These novel
imaging techniques are gaining traction and data are warranted to help in the early or
subclinical identification of cardiotoxicity in older patients. Currently, routine screening for
left ventricular systolic function remains the standard of care with echocardiography and
CMR as the imaging modalities of choice. MUGA is less preferable as the imaging modality
of choice for surveillance due to its use of ionizing radiation in a patient population that
requires serial studies. With 12 months of adjuvant trastuzumab as the standard of care, this
translates into a minimum of nine studies, associated with a significant dose of ionizing
radiation and the risk of radiation-related secondary cancers. A recent publication
highlighted this issue through the case of a patient with multiple myeloma who received 17

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 Reddy et al. Page 9

Author ManuscriptAuthor MUGAs, corresponding ManuscriptAuthor

ManuscriptAuthor to an effective radiation Manuscript
dose of 113 mSv, over a span of three years
(87).

Serum Biomarkers
High sensitivity troponin has been evaluated as a possible early predictor for cardiotoxicity
during cancer treatment (88–91). A study of 703 patients treated with high-dose
anthracyclines, evaluated the prognostic value of serial high-sensitivity cardiac troponin at
preset time points on start, 12, 24, 36, and 72 hours, and one month after each dose of
highdose anthracycline therapy (91). The incidence of cardiovascular events, defined as
heart failure, asymptomatic decline of left ventricular systolic function, and arrhythmias,
was noted at 87% in the group with both early and late troponin elevation, 37% with only
early elevated troponin and 1% with negative troponin values (91). A similar study in
patients receiving trastuzumab with troponin elevation identified those at risk for major
adverse cardiac events and irreversible cardiotoxicity (90, 92). The use of NT-proBNP has
been limited to clinically appropriate settings such as patients presenting with signs and
symptoms of heart failure (93). The evidence on the use of biomarkers in predicting patients
at risk for cardiotoxicity is limited and more studies are needed before recommendations are
made regarding routine use of biomarkers for surveillance including in older adults.

Treatment of Cardiotoxicity
Heart failure and cardiomyopathy from cancer treatments should be treated according to the
standard ACC/AHA guidelines for the evaluation and management of heart failure (94). This
generally includes the traditional mainstays of heart failure treatment: beta blockers,
ACEinhibitors, angiotensin II receptor blockers, aldosterone antagonists, and diuretics.
Exercise training and cardiac rehabilitation likely have similar efficacy in this group as well.

Summary
In conclusion, significant evidence suggests that older patients are more susceptible to
cancer-treatment related cardiotoxicity compared to their younger counterparts. Barriers
such as pre-existing comorbidities, the potential for undertreatment and under-representation
in clinical trials remain. There is a need for close collaboration between clinicians in a
multidisciplinary approach. Clinical studies are urgently needed on the prevention, early
detection, and treatment of cardiotoxicity in older cancer survivors.

Acknowledgments
This article was supported by National Institutes of Health grant K23HL132011-01 and the University of
Minnesota Clinical and Translational Science Institute KL2 Scholars Career Development Program Award
(National Institutes of Health grant KL2TR000113-05), both to Dr. Chetan Shenoy.

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Figure 1.
The “snowball effect” resulting in cardiovascular complications of cancer therapy in older
adults. See text for details. Adapted with permission from Shenoy et al. (13)

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